Clinical and biochemical risk factors for first and recurrent episodes of venous thrombosis Christiansen, S.C.

(1)

Christiansen, S.C.

Citation

Christiansen, S. C. (2010, September 28). Clinical and biochemical risk factors for first and recurrent episodes of venous thrombosis. Retrieved from https://hdl.handle.net/1887/15992

Version: Corrected Publisher’s Version License:

Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/15992

Note: To cite this publication please use the final published version (if applicable).

(2)

(3)

55

(4)

55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 7KHREMHFWLYHVRIWKLVWKHVLVZHUHWRVWXG\WKHPDJQLWXGHRIWKHULVNRIYHQRXVWKURPERVLV

LQWKHJHQHUDOSRSXODWLRQDQGWRGHWHUPLQHFOLQLFDODQGELRFKHPLFDOIDFWRUVWKDWLQÀXHQFH

WKLVULVN:HH[DPLQHGWKLVVHSDUDWHO\IRU¿UVWDQGIRUUHFXUUHQWWKURPERWLFHYHQWVDQGWKH

FRQWHQWRIWKHWKHVLVLVVSOLWDFFRUGLQJO\LQSDUWDQGSDUW:HXVHGGDWDIURPWZRVWXGLHV

IRUERWKREMHFWLYHV752/D1RUZHJLDQSURVSHFWLYHIROORZXSVWXG\LQWKHSRSXODWLRQLQ

ZKLFKZHFRXQWHGSDWLHQWVZLWKD^VWHYHQWRIYHQRXVWKURPERVLVDQG/(76DIROORZXSRID

'XWFKFRKRUWRIFRQVHFXWLYHSDWLHQWVZLWKD^VWREMHFWLYHO\FRQ¿UPHGYHQRXVWKURPERVLV

)LUVWZHHVWLPDWHGWKHLQFLGHQFHDQGPRUWDOLW\RID¿UVW97HYHQWLQDJHQHUDOSRSXODWLRQ

LHWKHUHVLGHQWVRI1RUG7U¡QGHODJFRXQW\LQ1RUZD\DJHG\HDUVDQGROGHUQ

)URPWKLVSRSXODWLRQZHLGHQWL¿HGDOOFDVHVZLWKDQREMHFWLYHO\YHUL¿HGGLDJQRVLVRI97WKDW

RFFXUUHGEHWZHHQDQG:HIRXQGSDWLHQWVZLWKD¿UVWGLDJQRVLVRI97GXULQJ

SHUVRQ\HDUVRIIROORZXS7KHLQFLGHQFHUDWHIRUDOO¿UVW97HYHQWVZDVSHU

SHUVRQ\HDUV&,7KHLQFLGHQFHUDWHVLQFUHDVHGH[SRQHQWLDOO\ZLWK

DJHDQGZHUHVOLJKWO\KLJKHULQZRPHQWKDQLQPHQ7KHGD\FDVHIDWDOLW\UDWHZDVKLJKHU

LQSDWLHQWVZLWK3(WKDQLQWKRVHZLWK'97YVULVNUDWLR&,

LWZDVDOVRKLJKHULQSDWLHQWVZLWKFDQFHUWKDQLQSDWLHQWVZLWKRXWFDQFHUYV

ULVNUDWLR&,FKDSWHU

$VD¿UVWIDFWRUWKDWFRXOGSRWHQWLDOO\LQÀXHQFHWKHRFFXUUHQFHRIWKURPERVLVZHH[DPLQHG

OHYHOV RI F\WRNLQHV )RUPHU VWXGLHV KDYH DVVRFLDWHG LQFUHDVHG OHYHOV RI LQÀDPPDWRU\

SDUDPHWHUVZLWKDQLQFUHDVHGULVNRIYHQRXVWKURPERVLV$VLQPRVWRIWKHVHVWXGLHVEORRG

ZDVVDPSOHGDIWHUWKHWKURPERWLFHYHQWWKHUHVXOWVZHUHSRWHQWLDOO\ELDVHGLIWKHRFFXUUHQFH

RIDWKURPEXVLWVHOILQLWLDWHVDQLQÀDPPDWRU\UHVSRQVH,QRXUSURVSHFWLYHGHVLJQ752/

VWXG\ZHIRXQGQRHYLGHQFHRIDQ\SUHH[LVWLQJLQÀDPPDWRU\VWDWHLQWKRVHZKRGHYHORSHG

D¿UVWHYHQWDVFRPSDUHGWRWKRVHZKRGLGQRWFKDSWHU1HYHUWKHOHVVLWFDQQRWEHIXOO\

UXOHGRXWWKDWKLJKOHYHOVRIF\WRNLQHVSUHGLVSRVHWR97DVWKHSURVSHFWLYHVWXG\KDVDVD

GUDZEDFNWKDWWKHUHDUHIRUPRVWLQGLYLGXDOVSURWUDFWHGWLPHSHULRGVEHWZHHQEORRGVDPSOLQJ

DQGWKURPERWLFHYHQW

,Q FKDSWHU ZH H[DPLQHG DQRWKHU ULVN IDFWRU IRU D ¿UVW YHQRXV WKURPERVLV LH WKH

SUHVHQFH RI DQWLFDUGLROLSLQ DQWLERGLHV DJDLQ LQ WKH752/ VWXG\ 3DWLHQWV ZLWK 6\VWHPLF

/XSXV(U\WKHPDWRGHVKDYHDQLQFUHDVHGULVNRIERWKYHQRXVDQGDUWHULDOWKURPERVLV7KHUH

KDVEHHQDSDUWLFXODULQWHUHVWLQWKHFDUULHUVKLSRIDQWLERGLHVGLUHFWHGDJDLQVWSKRVSKROLSLGV

7KH WULJJHU LQGXFLQJ WKH SURGXFWLRQ RI WKHVH DQWLERGLHV LV QRW ZHOO XQGHUVWRRG EXW LW LV

EHOLHYHG WR EH D IDLOXUH RI WKH UHJXODWRU\ PHFKDQLVPV RI WKH DXWRLPPXQH V\VWHP ,Q WKH

752/ZHGLGQRW¿QGHYLGHQFHWKDWDQWLFDUGLROLSLQDQWLERGLHVDUHULVNIDFWRUVIRUVXEVHTXHQW

YHQRXVWKURPERWLFGLVHDVHDOWKRXJKWKLVPD\EHGLIIHUHQWIRUKLJKWLWUHVH[FHHGLQJWKH^WK SHUFHQWLOHLQKHDOWK\FRQWUROVFKDSWHU

1H[WZHH[DPLQHGLQWKH752/VWXG\ZKHWKHUKLJKOHYHOVRIKRPRF\VWHLQHDUHDULVNIDFWRU

IRUD^VWHYHQWRIYHQRXVWKURPERVLVLQWKHJHQHUDOSRSXODWLRQ:HIRXQGWKDWKLJKOHYHOV

RIKRPRF\VWHLQHDUHDWPRVWDZHDNULVNIDFWRUIRUYHQRXVWKURPERVLV7KHVPDOOLQFUHDVHG

ULVNWKDWZHIRXQGLQPHQFRXOGKDYHEHHQWKHUHVXOWRIFRQIRXQGLQJE\FRPRUELGLW\WKDW

ZHZHUHQRWDEOHWRIXOO\DGMXVWIRUFKDSWHU,QDGGLWLRQWRWKLVQHJDWLYH¿QGLQJIRU

KRPRF\VWHLQH OHYHOV ZH DOVR IRXQG QR LQFUHDVHG ULVN IRU UHFXUUHQW 97 LQ SDWLHQWV ZLWK

K\SHUKRPRF\VWHLQHPLDLQWKH/(76FKDSWHU

(5)

55

,Q FKDSWHU ZH ORRNHG LQWR GHWDLO ZKHWKHU REHVLW\ LV UHODWHG WR $3&UHVLVWDQFH DQG

ZKHWKHUWKLVFRXOGEHPHGLDWHGE\LQFUHDVHGOHYHOVRIIDFWRU9,,,7KHUHVXOWVFRQ¿UPHGWKDW

WKLVZDVWKHFDVHDQGIXUWKHUPRUHWKDWIDFWRU9/HLGHQFDUULHUVKLSDGGVWRWKHULVNRIYHQRXV

WKURPERVLVLQREHVHDVFRPSDUHGZLWKQRQREHVHSDWLHQWV

,QSDUWZHIRFXVHGRQWKHLQFLGHQFHRIUHFXUUHQW97DQGLWVULVNIDFWRUVLQVXEMHFWVZLWKD

¿UVW97SDWLHQWVZKRSDUWLFLSDWHGLQWKH/(76VWXG\ZHUHIROORZHGIRUDPHDQRI

\HDUVDQGFRPSOHWHIROORZXSZDVDFKLHYHGLQSDWLHQWV5HFXUUHQFHRIWKURPERWLF

HYHQWVRFFXUUHGLQSDWLHQWVGXULQJDWRWDORISDWLHQW\HDUV7KHUDWHRIWKURPERWLFHYHQW

UHFXUUHQFHZDVSHUSDWLHQW\HDUV&,7KHULVNRIUHFXUUHQFHZDV

WLPHV&,KLJKHULQPHQWKDQLQZRPHQSDWLHQWVZKRVHLQLWLDOWKURPERWLF

HYHQWZDVLGLRSDWKLFKDGDKLJKHUULVNRIUHFXUUHQFHWKDQSDWLHQWVZKRVHLQLWLDOHYHQWZDV

SURYRNHG+5&,5HFXUUHQFHULVNZDVDOVRKLJKHUIRUZRPHQZKRXVHG

RUDOFRQWUDFHSWLYHVGXULQJIROORZXSSHUSDWLHQW\HDUV&,WKDQ

IRUWKRVHZKRGLGQRWSHUSDWLHQW\HDUV&,6XUSULVLQJO\WKHUHZDV

QRFOHDUUHODWLRQEHWZHHQUHFXUUHQFHULVNDQGWKHSUHVHQFHRIWKURPERSKLOLD&KDSWHU ,QFKDSWHUZHIRXQGWKDWPHQZLWKDQXQSURYRNHG¿UVWHYHQWKDGWKHKLJKHVWULVNRI

UHFXUUHQFHZLWKDOPRVWRQHWKLUGH[SHULHQFLQJDVHFRQGXQSURYRNHGHYHQWZLWKLQ\HDUV

,5SHUVRQ\HDUVIRUPHQZLWKDQXQSURYRNHG¿UVWDQGVHFRQGHYHQW7KLVULVN

ZDVIROGORZHULQZRPHQ,5SHUVRQ\HDUVKD]DUGUDWLR&, IRUPHQYVZRPHQ$JHKDGQRHIIHFWRQWKHUDWHRIXQSURYRNHGUHFXUUHQFHQRUKDGWLPH

HODSVHGVLQFHWKH¿UVWHYHQW,QZRPHQDOPRVWKDOIRIWKHUHFXUUHQFHVZHUHSURYRNHGDQG

RFFXUUHGPDLQO\GXULQJRUDOFRQWUDFHSWLYHXVHSUHJQDQF\RUSXHUSHULXP$GYLVLQJZRPHQWR

TXLWRUDOFRQWUDFHSWLRQDIWHUD¿UVWHYHQWVHHPVZDUUDQWHG&KDSWHU

,WKDVEHHQSURSRVHGWKDWWKHHQGRJHQRXVWKURPELQSRWHQWLDO(73FRXOGEHDXVHIXOWHVW

WRLGHQWLI\WKHJURXSRISDWLHQWVZKRDUHDWSDUWLFXODUULVNRIGHYHORSLQJUHFXUUHQWYHQRXV

WKURPERVLV 1HYHUWKHOHVV RXU VWXG\ VKRZHG WKDW WKH ULVN RI UHFXUUHQFH LQ SDWLHQWV ZLWK

LQFUHDVHG(73ZDVRQO\VOLJKWO\LQFUHDVHGDQGLWWKHUHIRUHVHHPVXQOLNHO\WKDWWKLVWHVWFDQ

LGHQWLI\SDWLHQWVDWDQLQFUHDVHGULVNRIUHFXUUHQFHFKDSWHU

/DVWO\DVULVNRIUHFXUUHQFHFRXOGEHLQFUHDVHGLQWKHMRLQWSUHVHQFHRIVHYHUDOULVNIDFWRUV

ZHVWXGLHGZKHWKHU)9/HLGHQFDUULHUVZKRDOVRKDYHKLJKOHYHOVRI)9,,,),;RU);,KDYH

DKLJKHUULVNRIDVHFRQGHYHQW7KHUHVXOWVRIRXUDQDO\VLVLQWKH/(76GDWDIDLOHGWRVKRZ

VXFKDQDVVRFLDWLRQFKDSWHU

6WXGLHV DLPHG DW LGHQWLI\LQJ LQGLYLGXDOV DW LQFUHDVHG ULVN RI ¿UVW RU UHFXUUHQW YHQRXV

WKURPERVLVUHPDLQRIWKHXWPRVWLPSRUWDQFHDQGZLOOKRSHIXOO\LQWKHIXWXUHOHDGWRORZHU

ULVNV RI WKURPERVLV WKDQ ZH IRXQG LQ RXU VWXG\ DV YHQRXV WKURPERVLV UHPDLQV D PDMRU

GLVDEOLQJDQGRIWHQIDWDOGLVHDVH